MK4MDD

Genetic/Epigenetic Locus Search Cross Data Search

Study Report

Reference

Citation	Frodl, 2010 PubMed
Full Info	Frodl, T., Reinhold, E., Koutsouleris, N., Donohoe, G., Bondy, B., Reiser, M., Moller, H.J. and Meisenzahl, E.M. (2010) Childhood stress, serotonin transporter gene and brain structures in major depression. Neuropsychopharmacology, 35, 1383-1390.

Study

Hypothesis or Background	The underlying neurobiology of major depression (MD) is likely to represent an interaction between genetic susceptibility and environmental factors such as stress. We investigated, in a multimodal high-resolution magnetic resonance imaging (MRI) genetic study, whether reduced hippocampal volumes and other brain alterations are associated with the tri-allelic polymorphism of the serotonin transporter and childhood stress in patients with MD and healthy subjects.
Sample Information	patients with MD and healthy subjects
Method Detail	Patients with MD and healthy participants were investigated using high-resolution MRI and genotyping for serotonin transporter polymorphism in the promoter region of the serotonin transporter gene (SLC6A4, 5-HTTLPR). Region of interest analysis of the hippocampus, whole-brain voxel-based morphometry (VBM), and assessment of childhood stress were carried out.
Method Keywords	magnetic resonance imaging (MRI); genotyping
Result	Patients carrying the risk S-allele developed smaller hippocampal volumes when they had a history of emotional neglect compared with patients who only had one risk factor (environmental or genetic). In patients, childhood stress also predicted further hippocampal white matter alterations independently from the genotype. Moreover, the left prefrontal cortex was smaller in patients, whereby childhood stress resulted in larger prefrontal volumes in those subjects carrying the non-risk L-allele, suggesting preventive effects.
Conclusions	The findings indicate that subjects with both environmental and genetic risk factors are susceptible to stress-related hippocampal changes. Structural brain changes due to stress represent part of the mechanism by which the illness risk and outcome might be genetically mediated.

Relationships reported by Frodl, 2010

Component A Approved Name (Name in Paper)	Component A Type	Component B Approved Name (Name in Paper)	Component B Type	Statistical Result	Relationship Description	Result Category (Positive/Negative))
Stress (childhood stress)	environment	Prefrontal cortex (prefrontal volumes)	brain morphology and function		childhood stress resulted in larger prefrontal volumes in those subjects carrying the non-risk L-allele, suggesting preventive effects.	Positive
Stress (stress)	environment	Prefrontal cortex (prefrontal cortex)	brain morphology and function		Moreover, the left prefrontal cortex was smaller in patients, whereby childhood stress resulted in larger prefrontal volumes in those subjects carrying the non-risk L-allele, suggesting preventive effects.	Positive
Stress (stress)	environment	Hippocampus (hippocampus)	brain morphology and function		In patients, childhood stress also predicted further hippocampal white matter alterations independently from the genotype	Positive
Stress (childhood stress)	environment	White matter (hippocampal white matter)	brain morphology and function		In patients, childhood stress also predicted further hippocampal white matter alterations independently from the genotype.	Positive
Hippocampus (hippocampal volumes)	brain morphology and function	SLC6A4 (serotonin transporter gene)	gene		Patients carrying the risk S-allele developed smaller hippocampal volumes when they had a history of emotional neglect compared with patients who only had one risk factor (environmental or genetic). I	Positive
MDD	syndrome	Child abuse (emotional neglect)	environment		Patients carrying the risk S-allele developed smaller hippocampal volumes when they had a history of emotional neglect compared with patients who only had one risk factor (environmental or genetic).	Positive
MDD	syndrome	Prefrontal cortex (prefrontal cortex)	brain morphology and function		Moreover, the left prefrontal cortex was smaller in patients, whereby childhood stress resulted in larger prefrontal volumes in those subjects carrying the non-risk L-allele, suggesting preventive effects.	Positive
MDD	syndrome	left prefrontal cortex (left prefrontal cortex)	brain morphology and function		the left prefrontal cortex was smaller in patients	Positive
Hippocampus (hippocampus)	brain morphology and function	SLC6A4 (SLC6A4)	gene		Patients carrying the risk S-allele developed smaller hippocampal volumes when they had a history of emotional neglect compared with patients who only had one risk factor (environmental or genetic)	Positive